4-(2-Chlorophenyl)-6-[3-(dimethylamino)-2-hydroxypropyl]-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione | 622856-52-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-(2-Chlorophenyl)-6-[3-(dimethylamino)-2-hydroxypropyl]-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
• 英文别名: 4-(2-Chlorophenyl)-6-[3-(dimethylamino)-2-hydroxypropyl]-9-hydroxypyrrolo[3,4-c]carbazole-1,3-dione
• CAS: 622856-52-4
• 化学式: C₂₅H₂₂ClN₃O₄
• 分子量: 463.92
• InChiKey: RRJZVKWSZFBVPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(2-chlorophenyl)-6-[2-hydroxy-3-(dimethylamino)propyl]-9-methoxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione 在 吡啶盐酸盐 作用下， 以165 mg的产率得到4-(2-Chlorophenyl)-6-[3-(dimethylamino)-2-hydroxypropyl]-9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
  参考文献：
  名称：

  Synthesis and structure–activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases

  摘要：

  A series of N-6 substituted 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones were prepared from N-substituted (5-methoxyphenyl)ethenylindoles. The target compounds were tested for their ability to inhibit the G2/M cell cycle checkpoint kinases, Wee1 and Chk1. Analogues with neutral or cationic N-6 side chains were potent dual inhibitors. Acidic side chains provided potent (average IC(50) 0.057 microM) and selective (average ratio 223-fold) Wee1 inhibition. Co-crystal structures of inhibitors bound to Wee1 show that the pyrrolo[3,4-c]carbazole scaffold binds in the ATP-binding site, with N-6 substituents involved in H-bonding to conserved water molecules. HT-29 cells treated with doxorubicin and then target compounds demonstrate an active Cdc2/cyclin B complex, inhibition of the doxorubicin-induced phosphorylation of tyrosine 15 of Cdc2 and abrogation of the G2 checkpoint.

  DOI：

  10.1016/j.ejmech.2007.07.016

文献信息

• [EN] INHIBITORS OF CHECKPOINT KINASES (WEE1 AND CHK1)<br/>[FR] INHIBITEURS DE CHECKPOINT KINASES (WEE1 ET CHK1)
  申请人：WARNER LAMBERT CO

  公开号：WO2003091255A1

  公开（公告）日：2003-11-06

  This invention relates to pyrrolocarbazole derivatives according formula (I) wherein R1, R2, r7, R8 R9, X and Y are as defined in the specification wherein said derivatives specifically inhibit one or both of the checkpoint kinases Wee1 and Chk1.

  本发明涉及公式（I）中的吡咯并咔唑衍生物，其中R1，R2，r7，R8，R9，X和Y如规范中所定义，其中所述衍生物特异性地抑制检查点激酶Wee1和Chk1中的一个或两个。
• INHIBITORS OF CHECKPOINT KINASES (WEE1 AND CHK1)
  申请人：WARNER-LAMBERT COMPANY LLC

  公开号：EP1501831A1

  公开（公告）日：2005-02-02
• US7094798B1
  申请人：——

  公开号：US7094798B1

  公开（公告）日：2006-08-22